Mesenchymal stromal cell-derived membrane particles: A novel cell-free therapy for inflammatory bowel diseases

• Published in: International immunopharmacology Vol. 118; p. 110076
• Main Authors: Serafini, Michele Aramburu, Sirena, Dienifer Hermann, da Silveira, Ana Beatriz Tittoni, Franco-da-Silva, Monique, Aubin, Mariana Rauback, Garcez, Tuane Nerissa Alves, Araújo, Anelise, dos Santos Pereira, Fernanda, Hoogduijn, Martin J., da Costa Gonçalves, Fabiany, Paz, Ana Helena
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2023
• Subjects: Animals; Cell-free therapy; Colitis - drug therapy; Colitis - therapy; Colon; Culture Media, Conditioned - pharmacology; Cytokines - therapeutic use; Dextran Sulfate; Disease Models, Animal; Immunomodulation; Inflammation; Inflammatory bowel diseases; Inflammatory Bowel Diseases - therapy; Inflammatory diseases; Mesenchymal Stem Cells; Mesenchymal stromal cells; Mesenchymal stromal cells membrane particles; Mice; Mice, Inbred C57BL; Ulcerative colitis; Inflammatory bowel diseases; Mesenchymal stromal cells membrane particles; Immunomodulation; Mesenchymal stromal cells; Cell-free therapy; Inflammatory diseases; Ulcerative colitis
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.110076

[Display omitted] •MSC membrane particles (MP) reduce disease activity in the colitis model.•MP balances Th1 and Th2 activity, modulating cytokine production.•MP prevents globet cell loss and maintain the colonic epithelial barrier function.•MP is a promising, safe and low-cost cell-free therapy for inflammatory diseases. Inflammatory bowel diseases (IBD), including ulcerative colitis, are chronic and idiopathic inflammations of the gastrointestinal tract. A disruption of the epithelial barrier and an imbalance between Th1 and Th2 subsets are associated with the onset and progression of these diseases. Mesenchymal stromal cells (MSC) are a promising therapy for IBD. However, cell-tracking studies have shown that intravenously infused MSC localize to the lungs and present short-term survival. To reduce practical complexities arising from living cells, we generated membrane particles (MP) from MSC membranes, which possess some of the immunomodulatory properties of MSC. This study investigated the effect of MSC-derived MP and conditioned media (CM) as cell-free therapies in the dextran sulfate sodium (DSS)-induced colitis model. Acute colitis was induced in C57BL/6 mice by oral administration of 2% DSS in drinking water ad libitum from days 0 to 7. Mice were treated with MP, CM, or living MSC on days 2 and 5. Our findings revealed that MP, CM, and living MSC ameliorated DSS-induced colitis by reducing colonic inflammation, the loss of colonic goblet cells, and intestinal mucosa permeability, preventing apoptosis of damaged colonic cells and balancing Th1 and Th2 activity. Therefore, MSC-derived MP have high therapeutic potential for treating IBD, overcoming the deficiencies of living MSC therapy, and opening novel frontiers in inflammatory diseases medicine.